Novel medicinal mushroom blend suppresses growth and invasiveness of human breast cancer cells
INTERNATIONAL JOURNAL OF ONCOLOGY
Authors: Jiang, Jiahua; Sliva, Daniel
Abstract
Mushrooms are an integral part of Traditional Chinese Medicine (TCM), and have been used for millennia to prevent or treat a variety of diseases Currently mushrooms or their extracts are used globally in the form of dietary supplements In the present study we have evaluated the anticancer effects of the dietary supplement MycoPhyto (R) Complex (MC), a novel medicinal mushroom blend which consists of a blend of mushroom mycelia from the species Agaricus blazei, Cordyceps sinensis, Coriolus verstcolor, Ganoderma lucidum, Grifola frondosa and Polyporus umbellatus, and beta-1,3-glucan isolated from the yeast, Saccharomyces cerevisiae Here, we show that MC demonstrates cytostatic effects through the inhibition of cell proliferation and cell cycle arrest at the G2/M phase of highly invasive human breast cancer cells MDA-MB-231 DNA-microarray analysis revealed that MC inhibits expression of cell cycle regulatory genes (ANAPC2, ANAPC2 BIRC5, Cyclin B1 Cychn H, CDC20 CDK2, CKS1B Cullin 1 E2F1 KPNA2 PKMYT1 and TFDP1) Moreover, MC also suppresses the metastatic behavior of MDA-MB-231 by the inhibition of cell adhesion, cell migration and cell invasion The potency of MC to inhibit invasiveness of breast cancer cells is linked to the suppression of secretion of the urokinase plasminogen activator (uPA) from MDA-MB-231 cells In conclusion, the MC dietary supplement could have potential therapeutic value in the treatment of invasive human breast cancer
Y-box binding protein 1 is up-regulated in proliferative breast cancer and its inhibition deregulates the cell cycle
INTERNATIONAL JOURNAL OF ONCOLOGY
Authors: Yu, Ying-Nan; Yip, George Wai-Cheong; Tan, Puay-Hoon; Thike, Aye Aye; Matsumoto, Ken; Tsujimoto, Masafumi; Bay, Boon-Huat
Abstract
The Y-box-binding protein 1 (YB-1), a member of the cold-shock domain RNA-and DNA-binding protein family, has pleiotropic functions such as regulation of the cell cycle. The aim of this study was to evaluate if YB-1 is a proliferative marker in breast cancer and elucidate potential downstream targets involved in YB-1-mediated cell cycle regulation using RNA interference technology. YB-1 protein expression was evaluated in tissue microarrays of 131 breast invasive ductal carcinomas by immunohistochemistry, while the YB-1 gene expression profile was evaluated in the T-47D, MDA-MB-231, ZR-75-1 and MCF7 breast cancer cell lines. Silencing of the YB-1 gene in T-47D breast cancer cells was performed using siRNA and the effects of clown-regulation of YB-1 on cell growth and regulation of the cell cycle were ascertained. A focused panel of 84 genes involved in cell cycle progression was also examined. In tissue microarrays. YB-1 expression was shown to be associated with proliferating cell nuclear antigen (PCNA) immunostaining.. siRNA-mediated silencing of the YB-1 gene inhibited cell proliferation and induced G1 phase cell cycle arrest in T-47D breast cancer cells. Knockdown of the YB-1 gene induced up-regulation of two genes which contribute to G I-arrest (RAD9A and CDKN3 genes) and down-regulation of ten genes associated with positive regulation of the cell cycle (SKP2, SUMO1, ANAPC4, CCNB1, CKS2, MNAT1, CDC20, RBBP8, KPNA2 and CCNC genes). The data obtained from the tissue microarrays and cell lines provide evidence that YB-1 is a reliable marker of cell proliferation and possibly a potential molecular target in breast cancer therapy.